IL13, CD14, pet and tobacco smoke influence atopy in 3 Dutch cohorts; The Allergenic study

¹ Dept of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
² Dept of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and Dept of paediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
³ Dept of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
⁴ Dept of paediatric Pulmonology, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, The Netherlands
⁵ Dept of Medical Microbiology, University Hospital Maastricht, Maastricht, The Netherlands
⁶ Dept of Epidemiology, Care and Public Health Research Institute and Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
⁷ Institute for Risk Assessment Sciences, University of Utrecht, and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
⁸ Dept of General Practice and Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands

^* To whom correspondence should be addressed. E-mail: d.s.postma{at}int.umcg.nl.

	Abstract

Studying gene-environment interactions may elucidate the complex origins of atopic diseases, yet requires large study populations. Pooling data from cohort studies may help, but may also obscure findings. We studied gene-environment interactions in atopy development and evaluated benefits of pooling data.

Haplotype tagging polymorphisms of Interleukin(IL)13 and CD14 were genotyped in 3,062 children from birth cohorts PIAMA, PREVASC and KOALA, and tested for association with total and specific IgE and interaction with tobacco smoke and pet exposure at ages 1,2,4, and 8 years by analysis of variance, ²-tests, and regression analyses.

IL13: At all ages, minor alleles of rs1295685 and rs20541 were associated with elevated IgE levels in pooled analyses (p<0.0001–0.03). CD14: The rs2569190-TT and rs2569191-CC genotypes associated with lower IgE and decreased risk of sensitisation at 4 and 8 years in children exposed to pets, with an opposite effect in non-exposed children (p-value for interaction:0.001–0.04). Findings for IL13 and CD14 were comparable in separate cohorts.

This study indicates that atopy is importantly influenced by IL13 at ages 1–8 years and by CD14 in interaction with pet exposure at ages 4 and 8. Pooling data improved effect estimates and genetic effects could be detected in interaction with important environmental factors.